Sara Abdeyazdan, Maryam Mohajeri, Sedigheh Saberi, Mahmoud Mirzaei, Seyed Abdulmajid Ayatollahi, Lotfollah Saghaei, Mustafa Ghanadian
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By performing regioselective synthesis, 7-O-paramethylbenzyl as an electron-donating group and 7-O-paranitrobenzyl as an electron-withdrawing group were added to quercetin, and, then, the synthesis of Sb(V) kaempferol and quercetin derivative complexes were performed using SbCl<sub>5</sub> solution in glacial acetic acid. The structures were confirmed by UV, ESI mass, IR, 1H-, and <sup>13</sup>C-NMR spectral data, and the Stoichiometry of the ligand-metal complex by the mole ratio method. Computational molecular modeling was conducted using the Gaussian program.</p><p><strong>Results: </strong>The structures were confirmed based on the results from UV, nuclear magnetic resonance (NMR), and electrospray ionization (ESI) mass analyses (3-12). Among the produced compounds, 11 and 12 as newly described, and other compounds as pre-defined compounds were identified. According to the results from biological test, kaempferol triacetate with more lipophilicity showed the highest anti-promastigote activity with an IC<sub>50</sub> value of 14.93 ± 2.21 µM. As for anti-amastigote activity, despite the differences, all antimony complexes showed anti-amastigote effects in vitro with IC<sub>50</sub> values of 0.52 to 14.50 µM.</p><p><strong>Conclusions: </strong>All flavonol Sb(V) complexes showed higher activity compared to meglumine antimonate in anti-amastigote effect. 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引用次数: 3
摘要
背景:近年来对利什曼病治疗的研究证实了黄酮醇和有机锑五价[(Sb(V))]配合物的抗寄生虫作用。目的:结合锑类化合物和黄酮醇的优点，并对其性质进行优化，寻找新的Sb(V)配合物。方法:采用吡啶乙酸酐制备山奈酚和过乙酸槲皮素。通过区域选择性合成，在槲皮素上加入7- o -参甲基苄基作为供电子基团和7- o -对硝基苄基作为吸电子基团，在冰醋酸中以SbCl5溶液合成Sb(V)山奈酚和槲皮素衍生物配合物。通过紫外、ESI质量、红外、1H-和13C-NMR谱数据对结构进行了确证，并通过摩尔比法对配-金属配合物进行了化学计量。采用高斯程序进行计算分子模拟。结果:通过紫外光谱(UV)、核磁共振(NMR)和电喷雾电离(ESI)质谱分析(3-12)对化合物的结构进行了确证。所得化合物中有11、12个为新描述化合物，其余为预定义化合物。生物学试验结果显示，亲脂性较强的三醋酸山奈酚抗promastigote活性最高，IC50值为14.93±2.21µM。在抗无尾螺旋体活性方面，尽管不同的锑配合物在体外均具有抗无尾螺旋体的作用，IC50值为0.52 ~ 14.50µM。结论:所有黄酮醇Sb(V)配合物的抗马马线虫作用均高于锑酸甲氨胺。在宿主巨噬细胞内，通过将复合物分解成锑和槲皮素或山奈酚类似物，观察到的抗寄生虫作用可能与Sb(V)/Sb(III)转化和类黄酮抗利什曼原虫活性有关。
Sb(V) Kaempferol and Quercetin Derivative Complexes: Synthesis, Characterization and Antileishmanial Activities.
Background: Recent studies on Leishmaniasis treatment have confirmed the antiparasitic effects of flavonols and organic antimony pentavalent [(Sb(V)] complexes.
Objectives: This study aimed to identify new Sb(V) complexes by combining the benefits of antimonials and flavonols as well as by optimizing their properties.
Methods: Kaempferol and quercetin peracetate were prepared using acetic anhydride in pyridine. By performing regioselective synthesis, 7-O-paramethylbenzyl as an electron-donating group and 7-O-paranitrobenzyl as an electron-withdrawing group were added to quercetin, and, then, the synthesis of Sb(V) kaempferol and quercetin derivative complexes were performed using SbCl5 solution in glacial acetic acid. The structures were confirmed by UV, ESI mass, IR, 1H-, and 13C-NMR spectral data, and the Stoichiometry of the ligand-metal complex by the mole ratio method. Computational molecular modeling was conducted using the Gaussian program.
Results: The structures were confirmed based on the results from UV, nuclear magnetic resonance (NMR), and electrospray ionization (ESI) mass analyses (3-12). Among the produced compounds, 11 and 12 as newly described, and other compounds as pre-defined compounds were identified. According to the results from biological test, kaempferol triacetate with more lipophilicity showed the highest anti-promastigote activity with an IC50 value of 14.93 ± 2.21 µM. As for anti-amastigote activity, despite the differences, all antimony complexes showed anti-amastigote effects in vitro with IC50 values of 0.52 to 14.50 µM.
Conclusions: All flavonol Sb(V) complexes showed higher activity compared to meglumine antimonate in anti-amastigote effect. Inside the host macrophages, by breaking down the complex into antimony and quercetin or kaempferol analogs, the observed antiparasitic effects may have been related to both Sb(V)/Sb(III) conversion and flavonoid antileishmanial activities.
期刊介绍：
The Iranian Journal of Pharmaceutical Research (IJPR) is a peer-reviewed multi-disciplinary pharmaceutical publication, scheduled to appear quarterly and serve as a means for scientific information exchange in the international pharmaceutical forum. Specific scientific topics of interest to the journal include, but are not limited to: pharmaceutics, industrial pharmacy, pharmacognosy, toxicology, medicinal chemistry, novel analytical methods for drug characterization, computational and modeling approaches to drug design, bio-medical experience, clinical investigation, rational drug prescribing, pharmacoeconomics, biotechnology, nanotechnology, biopharmaceutics and physical pharmacy.
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